Prognostic significance of fibrinogen and neutrophil/lymphocyte ratio score and D-dimer/Albumin ratio for prognosis in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Recent research indicates that systemic inflammation significantly affects the overall prognosis of individuals with aneurysmal subarachnoid hemorrhage. To delve deeper into this issue, a retrospective study was undertaken. The study aimed to investigate the relationship between fibrinogen and neutrophil/lymphocyte ratio scores, D-dimer/Albumin ratios, and the Glasgow Outcome Scale at 6 months post-discharge for patients with aSAH. METHODS: A retrospective analysis was conducted on 321 patients who experienced aneurysmal subarachnoid hemorrhage. These patients were monitored using the Glasgow Outcome Scale six months after being discharged from Huizhou Central People's Hospital. Patients with GOS scores between 1 and 3 were classified as having a poor prognosis, while those with scores ranging from 4 to 5 were considered to have a good prognosis. To create distinct sets, patients were randomly divided into both training and validation groups. The best cut-off value for the D-dimer/Albumin ratio was established through ROC curves, and the scores for fibrinogen and the neutrophil/lymphocyte ratio were calculated. Utilizing multivariate logistic regression analysis, independent risk factors linked to an unfavorable prognosis in aSAH patients were identified. A nomogram model was developed and validated based on these findings, providing an improved approach for evaluating the prognostic influence of risk factors. To gauge the model's predictive performance, several analytical tools such as ROC curves, calibration curves, and decision curve analysis were employed. This comprehensive approach ensured a thorough assessment of the prognostic prediction capabilities of the model. RESULTS: Multivariate regression analysis revealed that Age (OR=3.87, 95%CI=1.54-9.73, p=0.004), Pneumonia (OR=3.54, 95%CI=1.41-8.86, p=0.007), WFNS (OR=3.24, 95%CI=1.23-8.54, p=0.017), DAR (OR=2.88, 95%CI=1.13-7.34, p=0.027), and F-NLR (OR=3.12, 95%CI=1.22-7.97, p=0.017) were identified as independent risk factors influencing the prognosis of patients with aSAH. Additionally, the area under the ROC curve was 0.866 (95%CI=0.805-0.927) for the training set and 0.924 (95%CI=0.849-0.999) for the validation set. The calibration curve analysis demonstrated a minor error of 0.02 for the training set and 0.051 for the validation set. Furthermore, both the training set and validation set displayed significant clinical benefits according to the DCA curves, underscoring the meaningful utility of the developed nomogram. CONCLUSIONS: Fibrinogen and neutrophil/lymphocyte ratio scores, and the D-dimer/Albumin ratio emerged as significant independent risk factors for prognosticating the outcomes of patients with aSAH. Leveraging these factors, a robust nomogram model was meticulously developed, showcasing its impressive precision in prognostic predictions. These results underscore the promising clinical applicability of these biomarkers as effective prognostic indicators for individuals afflicted by aSAH.

Early long-term low-dosage colchicine and major adverse cardiovascular events in patients with acute myocardial infarction: a systematic review and meta-analysis.

Background: Current evidence on the efficacy and safety of colchicine after acute myocardial infarction (AMI) remains controversial. This study aims to clarify early low-dose long-term colchicine's exact efficacy and safety in AMI patients via more studies. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library databases for randomized controlled trials assessing the efficacy of colchicine on major adverse cardiovascular events (MACE) in recent AMI patients from inception to January 29, 2023, without any restriction. Additionally, we conducted subgroup analyses to assess the impact of early (≤3 days) long-term (≥1 year) low-dosage (0.5 mg/d) colchicine. Summary estimates were computed using Mantel-Haenszel and reported as risk ratios (RRs) or standard mean differences (SMDs), mean differences (MDs) with 95% confidence intervals (CIs). Sensitivity analyses were performed to explore the potential sources of heterogeneity. Review Manager software was used for the meta-analysis. Results: Eight studies identified from 564 screened records were analyzed, with 5,872 patients after AMI. The length of follow-up varied from five days to 22.7 months, and 0.5-1.0 mg colchicine was administered daily. In summary, compared to the control group, colchicine reduced the occurrence of MACE (RR, 0.56; 95% CI, 0.48-0.67) with 2.99-fold gastrointestinal adverse events in patients with recent AMI. Moreover, the relation referred to a gradual decrease in the occurrence of MACE with a longer follow-up duration (≥1 year) and lower dosage (0.5 mg/d) without leading more gastrointestinal adverse events. Colchicine decreased the follow-up levels of C-reactive protein (CRP) (MD -0.66, 95% CI, -0.98- -0.35) and neutrophils (SMD -0.22, 95% CI, -0.39- -0.55) when the follow-up period was 30 days. Conclusion: Early long-term low-dose colchicine decreases the risk of MACE via anti-inflammation without leading more gastrointestinal adverse events in patients with AMI.

Effect of intra-aortic balloon pump with veno-arterial extracorporeal membrane oxygenation in acute myocardial infarction with cardiogenic shock: A meta-analysis.

BACKGROUND: The effectiveness of a concomitant intra-aortic balloon pump (IABP) with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) intervention in acute myocardial infarction with cardiogenic shock (AMICS) patients is contested in the literature. This study sought to compare short-term mortality weaning rate from VA-ECMOin AMICS cases. METHODS: We conducted a literature review and compared the primary and secondary endpoints in the following treatment groups of AMICS patients: (1) VA-ECMO plus IABP vs. IABP alone and (2) VA-ECMO plus IABP vs. VA-ECMO alone. The primary endpoint was in-hospital all-cause mortality; while 30-days mortality, weaning from VA-ECMO, and vascular complications comprised secondary endpoints. RESULTS: VA-ECMO concomitant with IABP was administered to 3,580 (76.4%) patients, while IABP alone and VA-ECMO alone treatments accounted for 1.7% and 21.9% of the patients, respectively. We found that in-hospital mortality was significantly lower in patients treated with VA-ECMO plus IABP vs. VA-ECMO alone (odds ratio (OR) = 0.52; 95% Confidence Interval (CI) = 0.21-1.31; I-squared statistic (I2 = 30%) or IABP alone (OR = 0.20; 95% CI = 0.08-0.55; I2 = 0%). Additionally, 30-days mortality was significantly lower in patients treated with VA-ECMO plus IABP vs. VA-ECMO alone (OR = 0.31; 95% CI = 0.25-0.40; I2 = 0%) or IABP alone (OR = 0.24; 95% CI = 0.11-0.50; I2 = 0%). A significant difference was observed in weaning from VA-ECMO in patients treated with VA-ECMO plus IABP vs. VA-ECMO alone (OR = 1.91; 95% CI = 1.09-3.33; I2 = 0%). CONCLUSION: In-hospital and 30-days mortality were significantly lower in AMICS patients treated with VA-ECMO plus IABP vs. VA-ECMO alone or IABP alone. VA-ECMO with concomitant IABP could increase the proportion of patients weaned from VA-ECMO, significantly reducing in-hospital mortality, without increasing complications.

Multidisciplinary Guidelines for the Rational Use of Topical Non-Steroidal Anti-Inflammatory Drugs for Musculoskeletal Pain (2022).

(1) Background: Topical non-steroidal anti-inflammatory drugs (NSAIDs) are one of the primary drugs for treating musculoskeletal pain. However, there are currently no evidence-based recommendations about drug selection, drug administration, drug interactions, and use in special populations or other pharmacology-related content of such medications. To this end, the Chinese Pharmaceutical Association Hospital Pharmacy Professional Committee developed multidisciplinary guidelines on using topical NSAIDs to treat musculoskeletal pain. (2) Methods: The guidelines development process followed the World Health Organization guideline development handbook, the GRADE methodology, and the statement of Reporting Items for Practice Guidelines in Healthcare. The guideline panel used the Delphi method to identify six clinical questions to be addressed in the guidelines. An independent systematic review team conducted a systematic search and integration of evidence. (3) Results: Based on the balance between the benefits and harms of an intervention, the quality of the evidence, patient preferences and values, and resource utilization, the guideline panel developed 11 recommendations and nine expert consensuses on using topical NSAIDs to treat acute and chronic musculoskeletal pain. (4) Conclusions: Based on the effectiveness and overall safety of topical NSAIDs, we recommend patients with musculoskeletal pain use topical NSAIDs and suggest high-risk patients use topical NSAIDs, such as those with other diseases or receiving other concurrent treatments. The evidenced-based guidelines on topical NSAIDs for musculoskeletal pain incorporated a pharmacist perspective. The guidelines have the potential to facilitate the rational use of topical NSAIDs. The guideline panel will monitor the relevant evidence and update the recommendations accordingly.

Palladium-Catalyzed C-H Activation/Cyclization for the Synthesis of [60]Fullerene-Fused Phosphinolactones.

A novel and efficient palladium-catalyzed C-H activation reaction of [60]fullerene with arylphosphinic acids has been developed for the synthesis of [60]fullerene-fused phosphinolactones. A possible reaction mechanism is proposed to explain the generation of the obtained products. A representative product can be further electrochemically transformed into bis-benzylated 1,2- and 1,4-adducts of [60]fullerene. In addition, a [60]fullerene-fused phosphinolactone with a 12-membered ring can also be synthesized from the electrochemical ring expansion of the employed phosphinolactone with a 6-memebered ring with 1,2-bis(bromomethyl)benzene.

Systematic Risk Analysis of Semiconductor Global Market Based on Deep Feature Fusion K-Means Algorithm.

As the global semiconductor industry has entered a new round of rapid growth, it has also entered a golden cycle of economic growth. Semiconductor companies increase their intrinsic value through financing, industry mergers and acquisitions, and venture capital searches. At the same time, market investors pay more attention to the intrinsic value of companies when looking for good investment targets. Therefore, the systematic risk assessment of the global semiconductor market has become a common concern of market investors and corporate management. In this context, this paper found a method that can assess the systemic risk of the semiconductor global market, which is to use the K-means algorithm based on deep feature fusion. This paper analyzed the algorithm in depth, analyzed the quantum space of tensors, and used the definition of cluster fusion to obtain the relationship between the projection matrices U and V. Experiments were carried out on the improved algorithm, and market research was conducted on a multinational semiconductor company A, which mainly included the basic statistics of the rate of return and the ACF and PACF coefficients of the rate of return series. Finally, the stock risk comparison of company A and company B in the same period was carried out. The experimental results showed that comparing the three items of compound growth rate, coefficient of variation, and active rate coefficient, the highest compound growth rate was 0.41, which came from Category 2, the highest variation coefficient was 2.31, which came from Category 10, and the highest active rate coefficient was 1.78, which came from Category 9. The experimental content was completed well.

Copper-mediated synthesis of fullerooxazoles from [60]fullerene and N-hydroxybenzimidoyl cyanides.

A novel and efficient copper-mediated [3 + 2] heteroannulation reaction of [60]fullerene with N-hydroxybenzimidoyl cyanides has been developed for the synthesis of fullerooxazoles. A possible reaction mechanism involving unique C-CN and N-OH bond cleavages and subsequent C-OH bond formation for N-hydroxybenzimidoyl cyanides is proposed to explain the generation of fullerooxazoles. In addition, the formed fullerooxazoles can be further electrochemically transformed into amidated 1,2-hydrofullerenes.

A low-jitter timing generator based on completely on-chip self-measurement and calibration in a field programmable gate array.

This paper presents a high-stability and low-jitter Arbitrary Timing Generator (ATG) design based on the Xilinx Field Programmable Gate Array (FPGA) and its special integrated delay line. In recent years, FPGA-based or application specific integrated circuit-based delay lines have been used to achieve picosecond-level timing resolution. Devices with pure digital delay methods can only acquire triggers at the clock rising edges when triggered externally. Therefore, there is a large time irregularity caused by the uncertainty of the entry time of the trigger, which is difficult to compensate and leads to a large time jitter of outputs. We describe the design of an ATG that includes jitter self-measurement and calibration methods, which is available for both internal and external trigger modes. This structure is completely based on the FPGA's own resources and has the advantages of being simple and flexible. Experimental results show a sub-nanosecond timing resolution of 78 ± 20 ps with a minimum of 120 ps and a time jitter of 160 ± 20 ps in the external trigger mode after compensation.

[Impact of Tetracycline Antibiotic on the Transcriptional Expression of Tetracycline Resistance Genes in Shigella flexneri].

The tetracycline (TC) antibiotic has been widely found in different environmental matrices. The tetracycline resistant bacterium (TRB) of Shigella flexneri was screened and purified from activated sludge, and was then used to study the impact of TC stress on the gene abundances and expression levels of TC resistance genes (TC-ARGs), including tetC, tetO, and tetX, which were respectively quantified by quantitative PCR and reverse transcriptional PCR. Correlations between the TC concentration and gene abundances of TC-ARGs and their expression levels were discussed. The results showed that TC stress had an inhibiting effect on the growth of Shigella flexneri during the entire culture cycle (24 h) and that the growth rate of the bacterial concentration decreased with increasing TC concentration. However, less impact on the gene abundance of TC-ARGs was found. TC stress could promote the expression of TC-ARGs in Shigella flexneri, and the expression levels of tetC, tetO, and tetX genes first increased and then decreased. The correlation results indicated that no significant correlation was observed between the TC concentration and gene abundances of TC-ARGs and their expression levels. Nevertheless, the gene abundances of tetC and tetO were significantly correlated with their expression levels, thus indicating that they can be used to evaluate and assess expression levels to a certain extent.

SP1 activated-lncRNA SNHG1 mediates the development of epilepsy via miR-154-5p/TLR5 axis.

BACKGROUND: Epilepsy is a one of the most frequent serious neurological disorders characterized by enduring and unprovoked seizures. The treatments to epilepsy are very limited and many patients are even resistant to current medications due to the elusive pathogenesis. Here, we sought to investigate the functions of lncRNA SNHG1 and miR-154-5p in epilepsy. METHODS: We employed both in vivo mouse model and in vitro cell model to study epilepsy. H&E staining and Nissl staining were used to examine the morphology of hippocampus and measure neuronal injury, respectively. TUNEL staining and flow cytometry were performed to determine cell apoptosis. Caspase-3 activity assay kit was used to assess caspase-3 activity. RT-qPCR and western blot were conducted to measure the levels of SNHG1, miR-154-5p, TLR5, and SP1, respectively. Dual luciferase reporter assay was employed to validate the binding relationship of SNHG1/miR-154-5p and miR-154-5p/TLR5. ChIP assay was performed to confirm the transcriptional regulation of SP1 on SNHG1. RESULTS: Elevated SNHG1 and decreased miR-154-5p were observed in both in vivo mouse model and in vitro cell model of epilepsy. Knockdown of SNHG1 or transfection with miR-154-5p mimics significantly ameliorated Mg2+ free-induced neuronal injury in SH-SY5Y cells. SNHG1 acted as a sponge of miR-154-5p. Moreover, SNHG1 promoted neuronal injury via acting as a miR-154-5p sponge to disinhibit TLR5. Additionally, SP1 activated the transcriptional activity of SNHG1. CONCLUSION: In summary, SP1 transcriptionally activated-SNHG1 contributes to the development of epilepsy via directly regulating miR-154-5p/TLR5 axis, which provides novel targets in treatment of epilepsy.

Water temperature forecasting based on modified artificial neural network methods: Two cases of the Yangtze River.

Water temperature is a controlling indicator of river habitat since many physical, chemical and biological processes in rivers are temperature dependent. Highly precise and reliable predictions of water temperature are important for river ecological management. In this study, a hybrid model named BP_PSO3, based on the BPNN (back propagation neural network) optimized by the PSO (particle swarm optimization) algorithm, is proposed for water temperature prediction using air temperature (Ta), discharge (Q) and day of year (DOY) as input variables. The performance of the BP_PSO3 model was compared with that of the BP_PSO1 (with Ta as the input) and BP_PSO2 (with Ta and Q as the inputs) models to evaluate the importance of the inputs. In addition, a comparison among the BPNN, RBFNN (radial basis function neural network), WNN (wavelet neural network), GRNN (general regression neural network), ELMNN (Elman neural network), and BP_PSO-based models was carried out based on the MAE, RMSE, NSE and R2. The eight artificial intelligence models were examined to predict the water temperature at the Cuntan and Datong stations in the Yangtze River. The results indicated that the hybrid BPNN-PSO3 model had a stronger ability to forecast water temperature under both normal and extreme drought conditions. Optimization by the PSO algorithm and the inclusion of Q and DOY could help capture river thermal dynamics more accurately. The findings of this study could provide scientific references for river water temperature forecasting and river ecosystem protection.

Automatic Tunnel Steel Arches Extraction Algorithm Based on 3D LiDAR Point Cloud.

Automation is an inevitable trend in the development of tunnel shotcrete machinery. Tunnel environmental perception based on 3D LiDAR point cloud has become a research hotspot. Current researches about the detection of tunnel point clouds focus on the completed tunnel with a smooth surface. However, few people have researched the automatic detection method for steel arches installed on a complex rock surface. This paper presents a novel algorithm to extract tunnel steel arches. Firstly, we propose a refined function for calibrating the tunnel axis by minimizing the density variance of the projected point cloud. Secondly, we segment the rock surface from the tunnel point cloud by using the region-growing method with the parameters obtained by analyzing the tunnel section sequence. Finally, a Directed Edge Growing (DEG) method is proposed to detect steel arches on the rock surface in the tunnel. Our experiment in the highway tunnels under construction in Changsha (China) shows that the proposed algorithm can effectively extract the points of the edge of steel arches from 3D LiDAR point cloud of the tunnel without manual assistance. The results demonstrated that the proposed algorithm achieved 92.1% of precision, 89.1% of recall, and 90.6% of the F-score.

Repeated inhalation of sevoflurane inhibits the information transmission of Purkinje cells and delays motor development via the GABAA receptor ε subunit in neonatal mice.

General anesthesia is widely used in pediatric surgery, although the influence of general anesthesia on cerebellar information transmission and motor function is unclear. In the present study, neonatal mice received repeated inhalation of sevoflurane, and electrophysiological alterations in Purkinje cells (PCs) and the development of motor functions were detected. In addition, γ­aminobutyric acidA receptor ε (GABAA­R ε) subunit knockout mice were used to investigate the mechanism of action of sevoflurane on cerebellar function. In the neonatal mice, the field potential response of PCs induced by sensory stimulation and the motor function indices were markedly inhibited by sevoflurane, and the inhibitory effect was positively associated with the number of repetitions of anesthesia. In additional the GABAA­R ε subunit level of PCs was promoted by sevoflurane in a dose­dependent manner, and the inhibitory effects of sevoflurane on PC field potential response and motor function were alleviated in GABAA­R ε subunit knockout mice. The GABAA­R ε subunit was activated by sevoflurane, leading to inhibition of sensory information transmission in the cerebellar cortex, field potential responses of PCs and the development of cerebellar motor function. The present study provided experimental evidence for the safe usage of sevoflurane in clinical anesthesia, and suggested that GABAA­R ε subunit antagonists may be considered for combined application with general anesthesia with repeated inhalation of sevoflurane, for adverse effect prevention in the clinic.

Suppression of adipogenesis by pathogenic seipin mutant is associated with inflammatory response.

BACKGROUND: While pathogenic mutations in BSCL2/Seipin cause congenital generalized lipodystrophy, the underlying mechanism is largely unknown. In this study, we investigated whether and how the pathogenic missense A212P mutation of Seipin (Seipin-A212P) inhibits adipogenesis. METHODOLOGY/RESULTS: We analyzed gene expression and lipid accumulation in stable 3T3-L1 cell lines expressing wild type (3T3-WT), non-lipodystrophic mutants N88S (3T3-N88S) and S90L (3T3-S90L), or lipodystrophic mutant A212P Seipin (3T3-A212P). When treated with adipogenic cocktail, 3T3-WT, 3T3-N88S and 3T3-S90L cells exhibited proper differentiation into mature adipocytes, indistinguishable from control 3T3-L1 cells. In contrast, adipogenesis was significantly impaired in 3T3-A212P cells. The defective adipogenesis in 3T3-A212P cells could be partially rescued by either PPARγ agonist or PPARγ overexpression. Gene expression profiling by microarray revealed that inhibition of adipogenesis was associated with activation of inflammatory genes including IL-6 and iNOS. We further demonstrated that Seipin-A212P expression at pre-differentiation stages significantly activated inflammatory responses by using an inducible expression system. The inflammation-associated inhibition of adipogenesis could be rescued by treatment with anti-inflammatory agents. CONCLUSIONS: These results suggest that pathogenic Seipin-A212P inhibits adipogenesis and the inhibition is associated with activation of inflammatory pathways at pre-differentiation stages. Use of anti-inflammatory drugs may be a potential strategy for the treatment of lipodystrophy.

Seipin regulates excitatory synaptic transmission in cortical neurons.

Heterozygosity for missense mutations in Seipin, namely N88S and S90L, leads to a broad spectrum of motor neuropathy, while a number of loss-of-function mutations in Seipin are associated with the Berardinelli-Seip congenital generalized lipodystrophy type 2 (CGL2, BSCL2), a condition that is characterized by severe lipoatrophy, insulin resistance, and intellectual impairment. The mechanisms by which Seipin mutations lead to motor neuropathy, lipodystrophy, and insulin resistance, and the role Seipin plays in central nervous system (CNS) remain unknown. The goal of this study is to understand the functions of Seipin in the CNS using a loss-of-function approach, i.e. by knockdown (KD) of Seipin gene expression. Excitatory post-synaptic currents (EPSCs) were impaired in Seipin-KD neurons, while the inhibitory post-synaptic currents (IPSCs) remained unaffected. Expression of a shRNA-resistant human Seipin rescued the impairment of EPSC produced by Seipin KD. Furthermore, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced whole-cell currents were significantly reduced in Seipin KD neurons, which could be rescued by expression of a shRNA-resistant human Seipin. Fluorescent imaging and biochemical studies revealed reduced level of surface AMPA receptors, while no obvious ultrastructural changes in the pre-synapse were found. These data suggest that Seipin regulates excitatory synaptic function through a post-synaptic mechanism.

A novel septin-associated protein, Syp1p, is required for normal cell cycle-dependent septin cytoskeleton dynamics in yeast.

Septins are a family of GTP-binding proteins whose heterooligomeric complex is the basic structural element of the septin filaments found in many eukaryotic organisms. In budding yeast, septins are mainly confined at the mother-daughter junction and are required for cell morphogenesis and division. Septins undergo assembly and disassembly in accordance with the progression of the cell cycle. In this report, we identified the yeast protein Syp1p as a new regulator of septin dynamics. Syp1p colocalizes with septins throughout most of the cell cycle. Syp1p interacts with the septin subunit Cdc10p and can be precipitated by Cdc10p and Cdc12p. In the syp1Delta mutant, both formation of a complete septin ring at the incipient bud site and disassembly of the septin ring in later stages of cell division are significantly delayed. In addition, overexpression of Syp1p causes marked acceleration of septin disassembly. The fluorescence recovery after photobleaching (FRAP) assay further showed that Syp1p promotes septin turnover in different cell cycle stages. These results suggest that Syp1p is involved in the regulation of cell cycle-dependent dynamics of the septin cytoskeleton in yeast.

Three-dimensional vision with dual acousto-optic deflection encoding.

We report a new method of sensing a three-dimensional (3D) object surface with an arbitrary geometric shape. In this approach, the first-order beams diffracted from two acousto-optic deflectors (AODs) interfere with each other to form a spatial carrier that is used to encode the depth information from the 3D object surface. A direct digital synthesizer is utilized to control two AODs to generate sequentially spatial carriers with different spatial frequencies so that a modified temporal phase-unwrapping technique can be applied for decoding the shape information of the test surface. Preliminary experimental results are presented to demonstrate the effectiveness of this method.

Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways.

Axin uses different combinations of functional domains in down-regulation of the Wnt pathway and activation of the MEKK1/JNK pathway. We are interested in the elucidation of the functional switch of Axin. In the present study, we show that the Wnt activator CKIepsilon, but not CKIIalpha, Frat1, LRP5, or LRP6, inhibited Axin-mediated JNK activation. We also found that both CKIalpha and CKIepsilon interacted with Axin, whereas CKIIalpha did not bind to Axin and had no effect on Axin-mediated JNK activity even though CKIIalpha has also been suggested to be an activator for the Wnt pathway. The COOH-terminal region and the MEKK1-interacting domain of Axin are important for CKIalpha-Axin and CKIepsilon-Axin interaction. We further demonstrated that CKIepsilon and CKIalpha binding to Axin excluded MEKK1 binding, indicating that a competitive physical occupancy may underlie the inhibitory effect. Moreover, our data indicated that CKIepsilon kinase activity plays an additive role in this effect. Taken together, we have demonstrated that CKI and CKII exhibit differential effects on Axin-MEKK1 interaction and Axin-mediated JNK activation. Furthermore, our data suggest that CKI may provide a possible switch mechanism for Axin function in the regulation of Wnt and JNK pathways.